Analysis of the factors influencing moderate to poor performance status in patients with cancer after chemotherapy: a cross-sectional study comparing three models

There are no models for assessing the factors that determine moderate to poor performance status in patients with cancer after chemotherapy. This study investigated the influencing factors and identified the best model for predicting moderate–poor performance status. A convenience sampling method was used. Demographic and clinical data and evaluation results for fatigue, pain, quality of life and Eastern Cooperative Oncology Group status were collected three days after the end of chemotherapy. Decision tree, random forest and logistic regression models were constructed. Ninety-four subjects in the case group had moderate to poor performance status, and 365 subjects in the control group had no or mild activity disorders. The random forest model was the most accurate model. Physical function, total protein, general quality of life within one week before chemotherapy, hemoglobin, pain symptoms and globulin were the main factors. Total protein and hemoglobin levels reflect nutritional status, and globulin levels are an index of liver function. Therefore, physical function, nutritional status, general quality of life and pain symptoms within one week before chemotherapy and liver function can be used to predict moderate–poor performance status. Nurses should pay more attention to patients with poor physical function, poor nutritional status, lower quality of life and pain symptoms after chemotherapy.

There are many factors affecting patients' moderate and poor performance status, including sex and depression 11 .Health-related quality of life (HRQOL) is also related to moderate to poor performance status 12 .Patients undergoing chemotherapy often have distinct cognitive fatigue and evening physical fatigue profiles, which can lead to a moderate or poor performance status 13,14 .In addition, previous studies have shown that clinical stage, body mass index, lymphocyte count, and complications have an impact on cancer-related fatigue 15 .Therefore, there are many factors influencing moderate and poor performance status, and there may be interactions among various factors.Overall, physiological, psychological, social and other factors, such as fatigue, HRQOL, and pain, should be included in the analysis of moderate and poor performance status.
In addition, there are relevant theories to support this research hypothesis.In 2002, Armstrong analyzed the concept of symptom experience based on the analysis framework proposed by Walker and Avant and proposed the symptom experience model.According to this model, different symptoms are interrelated, and one symptom may promote the deterioration of another.The antecedents that affect symptoms include demographic characteristics (age, sex, etc.), disease characteristics (disease severity, treatment methods, comorbidities, and other clinical factors), and individual characteristics (health knowledge, psychological consistency, etc.), which can lead to different symptoms.The perception of symptoms also varies and includes the frequency, intensity, distress, and significance of symptoms 16 .Therefore, from the theory of symptom experience, demographic characteristics, disease characteristics and individual characteristics lead to different symptoms, so patients' experience of symptoms is different.Overall, the symptoms of patients during radiotherapy and chemotherapy are complex and interrelated.In clinical work, we should pay attention to the factors determining moderate to poor performance status, screen for common indicators, and lay the foundation for early intervention measures to prevent further development of symptoms leading to patient death.
The construction of models is more conducive to screening influencing factors.There are models for predicting speech, swallowing function and other aspects in oral cancer patients 17 and the risk of falls in elderly people with cancer 18 .However, no recent studies have derived models of the factors influencing the moderate to poor performance status of patients with cancer during chemotherapy.Therefore, it is necessary to further analyze the factors influencing common symptoms and clinical indicators of moderate to poor performance status during chemotherapy to better understand how symptoms develop.On the other hand, with the development of data mining technology and the maturity of statistical methods as well as the popularization of medical big data, an increasing number of researchers are attempting to use random forests and decision trees for disease diagnosis and complication prediction.These methods help to analyze the influencing factors more accurately.Moreover, in a preliminary effort, we applied three models to study the factors influencing moderate-to-severe cancer-related fatigue related to chemotherapy.The results indicated that the influencing factors and weights used to construct the optimal model were more accurate than those used in models derived from single-method research and can lay a better foundation for later intervention 19 .Therefore, this study enrolled Chinese patients with cancer to comprehensively analyze the factors and compare the three different models for predicting moderate and poor performance status.The validity and accuracy of the three models were evaluated to select the best model and to better identify the most important influencing factors and weights.

Design
To identify the factors influencing performance status, a cross-sectional study was performed.Information from a general information questionnaire, the Numerical Rating Scale (NRS), the Brief Fatigue Inventory (BFI) and the Eastern Cooperative Oncology Group (ECOG) performance status scale was collected 3 days after chemotherapy.Information on quality of life (QOL) was collected one day before chemotherapy to evaluate the quality of life of the subjects during the week before chemotherapy.Patients with ECOG scores of greater than or equal to 2 points were classified as the case group, and those with ECOG scores of less than or equal to 1 point were classified as the control group.Differences in the scores on the general information questionnaire, NRS, BFI and QOL were compared between the two groups.

Study participants
A convenience sampling method was used to select patients with cancer who experienced pain and were receiving chemotherapy from May 2022 to January 2023.The following inclusion criteria were applied: (1) patients and their families who volunteered to participate in the study and signed informed consent forms; (2) patients with basic language abilities; and 3) patients with clear consciousness and normal cognition.The following exclusion criteria were applied: (1) patients with other serious physical diseases; (2) patients who could not accurately express their ideas; (3) patients with other diseases, such as anemia, kidney function damage, or infection; (4) patients treated with steroids; and (5) patients without any cardiovascular or muscle diseases that affect activity.

Data collection
After receiving standard training, the members of the research group visited the bedside of the patients to administer the survey after providing consent from the ward manager.After providing informed consent from the patients, the questionnaire was distributed to the patients to explain the completion methods and matters needing attention.The investigators read the items and options for patients with disabilities.The digital questionnaire was completed based on patients' responses and collected on the spot.A total of 460 questionnaires were distributed.A total of 459 valid questionnaires were obtained.The effective recovery rate was 99.78%.One questionnaire was considered invalid based on the number of duplicate answers given for the two scales.www.nature.com/scientificreports/

General information questionnaire
The questionnaire gathers demographic and clinical data, including age, sex, diagnosis, marital status, education status, religion, income level, occupation, payment method, staging, weight loss within 3 months, location of pain, characteristics of pain, smoking history, the three levels of analgesic therapy and others.The three levels of analgesic therapy refer to the use of different levels of painkillers based on the level of pain.The first level mainly targets mild pain and mainly includes nonopioid drugs, such as nonsteroidal anti-inflammatory drugs, commonly including ibuprofen and aspirin.The second level is aimed mainly at relieving pain, and weak opioid drugs such as dihydrocodeine and tramadol are often used, with or without nonopioid drugs.The third level is mainly targeted at severe and persistent pain and involves the use of powerful opioid drugs such as morphine, methadone, and buprenorphine, with or without nonopioid drugs.Therefore, the three levels of the analgesic therapy principle can also reflect the patient's degree of pain.

Numerical Rating Scale (NRS)
The NRS is a standard instrument used in chronic pain studies.The pain digital score, calculated by 11-point digital scoring (pain intensity is described by increasing pain intensity starting with 0, which indicates no pain, to 10 points, which indicates the most severe pain), was used to assess the most severe pain levels in the past 24 h.After providing written informed consent, patients were instructed to draw a single mark on a horizontally oriented, graduated 10-cm NRS bounded by the descriptors "no pain'' at the far left and ''worst possible pain'' at the far right 20 .Previous studies have indicated that the most severe pain level in patients after chemotherapy in the past 24 h is strongly correlated with moderate to severe fatigue and poor quality of life 21 .Therefore, we believe that the degree of pain within 24 h may have an impact on fatigue, quality of life, and thus performance status.Moreover, to comprehensively evaluate the occurrence of pain and lay the foundation for future research, this study evaluated the NSR total score and the heaviest pain score at 24 h, 24-h minimum pain score, mean pain score and pain score at the time of investigation.

Brief fatigue inventory (BFI)
This questionnaire was designed to assess fatigue in patients with cancer and consists of 9 items rated on a Likert scale ranging from 0 (no fatigue) to 10 (severe fatigue) 22 .The average scores for these 9 items are reported as global fatigue scores (GFSs).Scores of 1-3, 4-6, and 7-10 were categorized as mild, moderate, and severe, respectively.The higher the score is, the more serious the fatigue.The first three items of the scale assess the current level of fatigue and the general and worst levels of fatigue in the past 24 h.The last six items assess the impact of fatigue on different aspects of life.The content included general activities, mood, walking, normal work, relationships with others and fun in life.The validity of the scale ranged from 0.81-0.92,and the internal consistency was 0.96.Wang et al., confirmed the validity of the Chinese version of the BFI for the assessment of cancer related fatigue in patients with cancer in China.The scale is simple and easy to understand and can distinguish the severity of fatigue 23 .

Quality of life scale developed by the European Organization for the Treatment and Research of Cancer (EORTCQLQ-C30)
This scale is the core scale for all patients with cancer, and it assesses 15 areas of QOL, for a total of 30 items.This scale can be used to evaluate five functional areas: physical function (PF) includes five items, role function (RF) includes two items, emotional function (EF) includes four items, cognitive function (CF) includes two items, and social function (SF) includes two items.There are three symptom areas.The fatigue (FA) symptom area includes three items, the nausea and vomiting (NV) symptom area includes two items, and the pain (PA) symptom area includes two items.There are six single items (each as an area): dyspnea (Dy) symptoms, sleep latency (SL) symptoms, appetite loss (AP) symptoms, constipation (CO) symptoms, diarrhea (DI) symptoms, economic difficulties (FI) and general QOL.Items 29 and 30 on the scale were divided into 7 grades.The grades ranged from 1 "very poor" to 7 "very good".The other items were divided into 4 grades and reverse scored: "no" (1 point), "a little bit" (2 points), "more" (3 points), and "very many" (4 points).The scores of each field were 0 ~ 100 after conversion.The higher the score was, the better the QOL.The score for each item in the Chinese version of the scale was strongly correlated with the score in the field (the R values were all greater than 0.5).The internal consistency reliability of each field was greater than 0.7, and the test-retest correlation coefficient was 0.7.Therefore, the Chinese version of the scale has good reliability and validity and can be used in this study 24 .

ECOG scoring criteria
The ECOG developed a simplified performance status score.The scale divides the activity status of patients into 6 levels: 0-5.A score of 5 indicates death.A score of 4 indicates that the individual cannot take care of himself or herself and cannot get out of bed.A score of 3 indicates that a person can take care of himself or herself partially and stay in bed for more than half a day.A score of 2 points means that the individual can take care of himself or herself but cannot hold a job and spends ≤ 50% of the day in bed.A score of 1 indicates that symptoms are mild and that light physical activity can be carried out.A score of 0 indicates that the performance status is completely normal.Therefore, a score of 2 or more is considered to indicate moderate to poor performance status, and a score of 2 or more indicates no or mild activity disorder 25 .Chemotherapy is generally considered to be unsuitable for patients with performance status levels 3 and 4.

Ethical considerations
The protocol for this observational study was prepared in accordance with the Helsinki Declaration and the Ethical Guidelines for Epidemiology Research (NIPH, 2014).Ethical approval was granted by the institutional review board (IRB) of the ethics committee (NO: 2021-98).All patients were informed of the nature and purpose of the study in writing and orally and provided informed consent to participate.If discomfort occurred during the study, the researcher suspended the study and dealt with it promptly.This research will provide necessary suggestions for patient treatment.The data gathered will also be helpful for diagnosing the disease or providing useful information for research on the disease.This study did not add any additional medical expenses to the subjects.All costs were borne by this project.All the members of the research team were assured that the information on the research subjects was confidential.When the results of this study are published, no personal data from the study subjects will be disclosed.All the researchers were trained accordingly.In the process of collecting the data, the research object was not included to ensure the objectivity of the data.

Data analysis
All the data were entered and checked by two researchers.Descriptive statistics were used to characterize the patients.The mean scores for each of the 9 BFI items were calculated to produce GFSs, for which mean values were obtained.Summary statistics were produced for pain (NRS), QOL (EORTCQLQ-C30) and CRF (BFI).First, we encoded the data, such as "diagnosis", "pain location", "pain nature" and "weight loss within 3 months", and converted the string data into numerical data.Second, individuals with ECOG scores of greater than or equal to 2 points were classified as the case group, and those with ECOG scores of less than or equal to 1 point were classified as the control group.We marked the case group as 1 and the control group as 0. Through the above steps, we obtained the final training data for statistical analysis.
In this model, LASSO regression was used for preliminary screening of variables.The variable whose coefficient is not 0 when lambda = 1 se was selected.Then, logistic regression, decision tree and random forest models were used for modeling.The internal validation method was used for validation, and the prediction effect of each model was evaluated based on the receiver operating characteristic (ROC) curve.
We used the caret package of R 4.1.2to model the decision tree and random forest model and optimize the superparameter maxdepth of the decision tree.The superparameters mtry, splitrule, and min.node.size of the random forest model were also optimized.
The influencing factors were defined as those in the model with the highest accuracy.The top 5 factors were described from heavy to light according to the weights that the model assigned to them.

Validity, reliability and rigor
All the data were collected according to the patients' answers while ensuring the patients' complete understanding.Those with too many regular answers were eliminated.Therefore, the accuracy of the data was guaranteed.All the data were entered and checked by two researchers.The accurate conversion of data involved three steps.All steps were double input and checked by two people.

Sample characteristics
A total of 94 subjects in the case group had moderate to severe activity disorders, and 365 subjects in the control group had no or only mild activity disorders.The demographic and clinical characteristics of all participants are summarized in Table 1.

Logistic regression
Based on LASSO regression, the following variables with coefficients of 0 were selected: age, diagnosis, stage, marital status, educational status, religion, income level, occupation, location of pain, characteristic of pain, alcoholism history, pain frequency, 24-h minimum pain, NRS total score, three levels of analgesic therapy, potassium, total protein, globulin, leukocyte count, neutrophil count, hemoglobin, general quality of life, physical function, pain and diarrhea symptoms.Based on the variables screened by LASSO regression, we carried out logistic regression modeling, used the AIC to establish a logistic regression model, and finally carried out a collinearity test to eliminate the variables with collinearity.After the VIF test, the VIF values of all variables were less than 2, indicating that there was no multicollinearity (Table 2).The area under the ROC curve (AUC) of the logistic regression model was 0.875.After the verification of bootstrap internal sampling (1000 times), the 95% confidence interval (95% CI) of the area under the curve (AUC) was 0.8303-0.9112,and the significance level was P < 0.01 (Fig. 1).The Hosmer-Lemeshow test results showed that P = 0.080377 (x 2 = 14.054, df = 8).The sensitivity was 88.3%.The specificity was 73.2%.The maximum value of the Youden index was 0.615.According to this model, the accuracy rate for predicting moderate-poor performance status was 45.9%, and the total accuracy was 76.3%.

Decision tree model
In this study, the growth level of the decision tree was 8, and the number of nodes was 12.Total protein, 24-h minimum pain, three levels of analgesic therapy, globulin and age were the most important influencing factors.The AUC of the decision tree model was 0.949, and the 95% confidence interval was 0.9114-0.9734.The sensitivity was 88.30%.The specificity was 95.6%.The maximum Youden index was 0.839.According to this model, the accuracy rate for patients with moderate-poor performance status was 83.8%, and the total accuracy rate was 94.1% (Figs. 2 and 3).www.nature.com/scientificreports/

Random forest model
Total protein, general quality of life, hemoglobin, pain symptoms and globulin were the most important influencing factors according to the random forest model.The AUC of the random forest model was 0.999, and the 95% confidence interval was 0.9929-1.000.The sensitivity was 98.9%.The specificity was 99.2%.The maximum value of the Yoden index was 0.981.According to this model, the accuracy of the model for moderate-to-poor performance status was 98.9%, and the total accuracy was 99.6% (Fig. 4).

Model comparison
A comparison of the three models revealed that the accuracy and AUC differed among the three models (Table 3), and the differences in AUC values among the regression model, decision tree model and random forest model were statistically significant (P < 0.05) (Table 4, Fig. 5).The random forest model was the best model.Physical function, total protein, general quality of life within one week before chemotherapy, hemoglobin, pain symptoms and globulin were the main factors associated with moderate or poor performance status (Fig. 6, Table 5).

Discussion
The performance status is also a very important indicator of patient performance during chemotherapy and can directly indicate whether chemotherapy can proceed normally.However, little is known about the influencing factor model of moderate to severe performance status until now 26 .In this study, three statistical methodsrandom forest, logistic regression and decision tree-were used to construct the influencing factor models.Through model comparison, the best model was selected to determine which influencing factors and weights were most accurate to improve the reliability of the results.The results showed that the random forest model had the highest accuracy.The accuracy rate reached 0.996, which was much greater than the accuracy standard of 0.8 27 .Therefore, the model can be used to determine the influencing factors.The random forest is calculated by using the overall data.In machine learning, a random forest is a classifier containing multiple decision trees, and its output category is determined by the mode of the category output by individual trees.The main features are as follows: for many kinds of data, high-accuracy classifiers can be produced 28 .Therefore, many input variables can be processed.When determining the category, the importance of variables can be evaluated.Therefore, the efficiency of random forest prediction is more accurate than that of decision tree prediction 29 .The results of this study showed that physical function, pain and general quality of life in the week before chemotherapy and total protein, hemoglobin and globulin were factors influencing moderate to poor performance status within 3 days after starting chemotherapy in patients with cancer.The absolute importance of the six factors was above 40%.First, physical function, whose standardized importance was 14.14%, was the most important factor affecting the performance status of the body according to both the decision tree and random forest models.These results are in line with those of another study 30 .The patients' physical functions mainly included dressing, eating, walking, basic self-care ability, and physical labor, which are important components of quality of life 31 .Physical function can affect the overall physical condition, living ability, and working ability of the body 32 .Many studies have focused on interventions for patients' physical function.Among them, exercise intervention and nutritional support are the most common, accurate, and effective methods 33,34 .We suggest that further clinical research be conducted on how to strengthen patients' exercise compliance and improve their nutritional status during chemotherapy.This is extremely important for ensuring the normal progression of the treatment regimen.Second, total protein had important physiological functions in the body according to both the decision tree model and the random forest model.The determination of total serum protein is an important step in clinical biochemical tests.Serum proteins have many functions, such as maintaining normal colloidal osmotic pressure and maintaining the pH of the blood, transporting a variety of metabolites, regulating the physiological function of transported substances, and relieving toxicity, immunity and nutrition.Therefore, total protein can reflect the immune and nutritional status of the body 35 .This result is in line with many other studies.Studies have used preoperative performance status to predict postoperative complications and mortality in patients with colorectal cancer and have shown that preoperative nutritional status has a significant impact on preoperative performance status 36 .Other studies have used nutritional status to predict the prognosis of gastric cancer patients.Their results indicated that nutritional status can predict the prognosis of gastric cancer patients by affecting performance status 37 .Therefore, nutritional status plays an important role in performance status.Second, pain in the week before chemotherapy is also an important factor influencing a moderate-poor performance status.Pain is a common symptom among patients with cancer.It has been reported that pain affects patients' ability to perform normal physical exercise, exhibit cognitive rehabilitation and participate in social interactions and thus hinders daily function 38 .Therefore, the interaction between common symptoms of cancer can lead to poor performance status.This result is again in line with the results of other studies 39 .One study revealed that the performance status was significantly improved by administering ultrahigh doses of morphine to control pain.The evidence indicates the important role of pain in performance status 40 .However, the study also revealed that postchemotherapy pain did not significantly impact the performance status.One possible reason is that during the hospitalization observation period after chemotherapy, physical complications such as pain can be treated in a timely manner.This finding also demonstrates the importance of symptom management during home stays during chemotherapy periods.Therefore, more attention should be given to home symptom management during chemotherapy in the future.Moreover, general quality of life within one week before chemotherapy was the most important influencing factor for moderate to poor performance status in patients with cancer.Quality of life is a comprehensive reflection of individual physiological, psychological, and social conditions.It has an important impact on the decline in chemotherapy-related body function.These findings indicate that physiological, psychological, and social functions can all impact the decline in chemotherapy-related performance status during the interval between chemotherapy regimens, a conclusion that agrees with those of other studies.Several studies have shown that the factors influencing the performance status of patients during chemotherapy for breast cancer include age, psychological distress, cognitive performance, fatigue, anorexia, insomnia, pain and constipation 41 .The results suggested that nurses should pay attention to improving the quality of life and common symptoms of patients with cancer during chemotherapy intervals.For example, a nondrug and drug combination intervention mode can be used to actively treat chemical complications, help patients improve their self-care ability and maintain good interpersonal relationships through communication with their families to minimize the impact of complications on the body 42 .In addition, hemoglobin is an indicator of nutritional status.The nutritional status of the body is an important predictor of the performance status.Combined with the total protein results, it can be inferred that nutritional status is an important factor influencing moderate to poor performance status.Therefore, improving patients' nutritional status during the treatment interval is not only helpful for improving the physiological health of patients but also highly important for reducing complications during the next chemotherapy cycle.However, in clinical practice, chemotherapy patients often suffer from different degrees of nutritional disorders due to nausea, vomiting, anorexia and other reasons.It is suggested that diet plans or lists of chemotherapy patients should be formulated more scientifically in clinical work to help patients better cope with disease and treatment.Finally, this study provides the new discovery that globulin levels can also predict poor performance status to some extent.Globulin levels are an important index of liver function.When liver function is impaired, the level of globulin increases.Patients with impaired liver function can also experience symptoms such as fatigue, resulting in poor performance status.These results also suggest that we should pay attention to the effect of chemotherapy on patients' liver function in future work.When the indices of liver function are abnormal, special attention should be given to whether the patient has poor performance status.

Conclusion
This study analyses the factors influencing moderate-poor performance status by screening and comparing the results of different models.The random forest model has the highest accuracy.Physical function, nutritional status, quality of life within one week before chemotherapy, abnormal liver function, and pain symptoms all contribute to moderate or poor performance status.In clinical work, attention should be given to improving exercise compliance and nutritional support during chemotherapy intervals, with a focus on patients with poor nutritional status during chemotherapy, overall poor quality of life in the week before chemotherapy, pain, and liver function problems.In future research, the sample size should be increased, and a more comprehensive drug and nondrug intervention program should be explored to help patients improve their physical and psychological conditions through physiological, psychological, social and other aspects to cope with chemotherapy-related complications during the course of chemotherapy.

Ethical approval and consent to participate
The protocol for this study was prepared in accordance with the Helsinki Declaration and the Ethical Guidelines for Epidemiology Research.Ethical approval was granted by the ethics committee of Fujian Cancer Hospital & Fujian Medical University Cancer Hospital (SQ2018-039-01).All patients were informed of the nature and purpose of this study, in writing and orally, and provided informed consent to participate in the study.

Figure 1 .
Figure 1.ROC curve of the logistic regression model.

Figure 2 .
Figure 2. Results of the decision tree model.

Figure 3 .
Figure 3. ROC curve of the decision tree model.

Figure 4 .
Figure 4. ROC curve of the random forest model.

Figure 5 .
Figure 5. Area under the ROC curve (AUC) of the three models.

Figure 6 .
Figure 6.Importance of variables in random forests.

Table 1 .
Patient characteristics in the two groups.Note: X±S: Mean ± standard deviation.

Table 2 .
The results of the logistics regression model.

Table 3 .
Prediction accuracy and AUC of three models.

Table 4 .
Pairwise comparison results of three models.

Table 5 .
The importance of the six most important variables in random forests.